Cited by 156Single-cell and spatial transcriptomicsGenomics and Chromatin DynamicsGenetics and Neurodevelopmental Disorders

Developmental regulation of human cortex transcription and its clinical relevance at single base resolution

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Jaffe, Andrew E, Shin, Jooheon, Collado-Torres, Leonardo, Leek, Jeffrey T, Tao, Ran, Li, Chao, Gao, Yuan, Jia, Yankai +4 more·2015·Nature Neuroscience

Abstract

Transcriptome analysis of human brain provides fundamental insight into development and disease, but it largely relies on existing annotation. We sequenced transcriptomes of 72 prefrontal cortex samples across six life stages and identified 50,650 differentially expression regions (DERs) associated with developmental and aging, agnostic of annotation. While many DERs annotated to non-exonic sequence (41.1%), most were similarly regulated in cytosolic mRNA extracted from independent samples. The DERs were developmentally conserved across 16 brain regions and in the developing mouse cortex, and were expressed in diverse cell and tissue types. The DERs were further enriched for active chromatin marks and clinical risk for neurodevelopmental disorders such as schizophrenia. Lastly, we demonstrate quantitatively that these DERs associate with a changing neuronal phenotype related to differentiation and maturation. These data show conserved molecular signatures of transcriptional dynamics across brain development, have potential clinical relevance and highlight the incomplete annotation of the human brain transcriptome.

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Authors
Jaffe, A. E., Shin, J., Collado-Torres, L., Leek, J. T., Tao, R., Li, C., Gao, Y., Jia, Y., Maher, B. J., Hyde, T. M., Kleinman, J. E., & Weinberger, D. R.
Affiliations
Johns Hopkins University (US)
Corresponding author
  • Jaffe, Andrew E
  • Weinberger, Daniel R
Venue
Nature Neuroscience
Published
2014-12-15
Volume
18
Issue
1
Pages
154-161
ISSN
  • 1097-6256 (ISSN-L)
  • 1546-1726
OpenAlex
W2002097805
Cited by
156
References
63
Citations by year
2026: 7 · 2025: 6 · 2024: 7 · 2023: 10 · 2022: 5 · 2021: 4 · 2020: 20 · 2019: 19 · 2018: 18 · 2017: 20 · 2016: 27 · 2015: 13
FWCI
8.21
Type
journal article
Language
en
Open access
Locations
  • Nature Neuroscience (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institute of Mental Health (R03MH096539, R21MH102791)
  • National Institute of General Medical Sciences (R01GM105705)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
Keywords
human prefrontal cortex, brain development, brain aging, transcriptome annotation, neurodevelopmental disorders, schizophrenia, mouse cortex, neuronal differentiation, neuronal maturation
MeSH terms
Aging, Animals, Cerebral Cortex, Chromatin, Female, Fetus, Humans, Infant, Infant, Newborn, Neurons, Pregnancy, Conserved Sequence, Gene Expression Regulation, Developmental, Mice, Transcriptome

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